"""
A collection of density physical property definitions.
"""
from propertyestimator.properties import PhysicalProperty
from propertyestimator.properties.plugins import register_estimable_property
from propertyestimator.protocols import coordinates, forcefield, simulation, miscellaneous
from propertyestimator.substances import Substance
from propertyestimator.workflow.schemas import WorkflowSchema
from propertyestimator.workflow.utils import ProtocolPath
[docs]@register_estimable_property()
class HostGuestBindingAffinity(PhysicalProperty):
"""A class representation of a host-guest binding affinity property"""
@property
def multi_component_property(self):
"""Returns whether this property is dependant on properties of the
full mixed substance, or whether it is also dependant on the properties
of the individual components also.
"""
return False
[docs] @staticmethod
def get_default_workflow_schema(calculation_layer, options=None):
if calculation_layer == 'SimulationLayer':
return HostGuestBindingAffinity.get_default_simulation_workflow_schema(options)
return None
[docs] @staticmethod
def get_default_simulation_workflow_schema(options=None):
"""Returns the default workflow to use when estimating this property
from direct simulations.
Parameters
----------
options: WorkflowOptions
The default options to use when setting up the estimation workflow.
Returns
-------
WorkflowSchema
The schema to follow when estimating this property.
"""
schema = WorkflowSchema(property_type=HostGuestBindingAffinity.__name__)
schema.id = '{}{}'.format(HostGuestBindingAffinity.__name__, 'Schema')
# Initial coordinate and topology setup.
filter_ligand = miscellaneous.FilterSubstanceByRole('filter_ligand')
filter_ligand.input_substance = ProtocolPath('substance', 'global')
filter_ligand.component_role = Substance.ComponentRole.Ligand
# We only support substances with a single guest ligand.
filter_ligand.expected_components = 1
schema.protocols[filter_ligand.id] = filter_ligand.schema
# Construct the protocols which will (for now) take as input a set of host coordinates,
# and generate a set of charges for them.
filter_receptor = miscellaneous.FilterSubstanceByRole('filter_receptor')
filter_receptor.input_substance = ProtocolPath('substance', 'global')
filter_receptor.component_role = Substance.ComponentRole.Receptor
# We only support substances with a single host receptor.
filter_receptor.expected_components = 1
schema.protocols[filter_receptor.id] = filter_receptor.schema
# Perform docking to position the guest within the host.
perform_docking = coordinates.BuildDockedCoordinates('perform_docking')
perform_docking.ligand_substance = ProtocolPath('filtered_substance', filter_ligand.id)
perform_docking.receptor_coordinate_file = ProtocolPath('receptor_mol2', 'global')
schema.protocols[perform_docking.id] = perform_docking.schema
# Solvate the docked structure using packmol
filter_solvent = miscellaneous.FilterSubstanceByRole('filter_solvent')
filter_solvent.input_substance = ProtocolPath('substance', 'global')
filter_solvent.component_role = Substance.ComponentRole.Solvent
schema.protocols[filter_solvent.id] = filter_solvent.schema
solvate_complex = coordinates.SolvateExistingStructure('solvate_complex')
solvate_complex.max_molecules = 1000
solvate_complex.substance = ProtocolPath('filtered_substance', filter_solvent.id)
solvate_complex.solute_coordinate_file = ProtocolPath('docked_complex_coordinate_path', perform_docking.id)
schema.protocols[solvate_complex.id] = solvate_complex.schema
# Assign force field parameters to the solvated complex system.
build_solvated_complex_system = forcefield.BuildSmirnoffSystem('build_solvated_complex_system')
build_solvated_complex_system.force_field_path = ProtocolPath('force_field_path', 'global')
build_solvated_complex_system.coordinate_file_path = ProtocolPath('coordinate_file_path', solvate_complex.id)
build_solvated_complex_system.substance = ProtocolPath('substance', 'global')
build_solvated_complex_system.charged_molecule_paths = [ProtocolPath('receptor_mol2', 'global')]
schema.protocols[build_solvated_complex_system.id] = build_solvated_complex_system.schema
# Solvate the ligand using packmol
solvate_ligand = coordinates.SolvateExistingStructure('solvate_ligand')
solvate_ligand.max_molecules = 1000
solvate_ligand.substance = ProtocolPath('filtered_substance', filter_solvent.id)
solvate_ligand.solute_coordinate_file = ProtocolPath('docked_ligand_coordinate_path', perform_docking.id)
schema.protocols[solvate_ligand.id] = solvate_ligand.schema
# Assign force field parameters to the solvated ligand system.
build_solvated_ligand_system = forcefield.BuildSmirnoffSystem('build_solvated_ligand_system')
build_solvated_ligand_system.force_field_path = ProtocolPath('force_field_path', 'global')
build_solvated_ligand_system.coordinate_file_path = ProtocolPath('coordinate_file_path', solvate_ligand.id)
build_solvated_ligand_system.substance = ProtocolPath('substance', 'global')
schema.protocols[build_solvated_ligand_system.id] = build_solvated_ligand_system.schema
# Employ YANK to estimate the binding free energy.
yank_protocol = simulation.LigandReceptorYankProtocol('yank_protocol')
yank_protocol.thermodynamic_state = ProtocolPath('thermodynamic_state', 'global')
yank_protocol.number_of_iterations = 2000
yank_protocol.steps_per_iteration = 500
yank_protocol.checkpoint_interval = 10
yank_protocol.verbose = True
yank_protocol.force_field_path = ProtocolPath('force_field_path', 'global')
yank_protocol.ligand_residue_name = ProtocolPath('ligand_residue_name', perform_docking.id)
yank_protocol.receptor_residue_name = ProtocolPath('receptor_residue_name', perform_docking.id)
yank_protocol.solvated_ligand_coordinates = ProtocolPath('coordinate_file_path', solvate_ligand.id)
yank_protocol.solvated_ligand_system = ProtocolPath('system_path', build_solvated_ligand_system.id)
yank_protocol.solvated_complex_coordinates = ProtocolPath('coordinate_file_path', solvate_complex.id)
yank_protocol.solvated_complex_system = ProtocolPath('system_path', build_solvated_complex_system.id)
schema.protocols[yank_protocol.id] = yank_protocol.schema
# Define where the final values come from.
schema.final_value_source = ProtocolPath('estimated_free_energy', yank_protocol.id)
# output_to_store = WorkflowOutputToStore()
#
# output_to_store.trajectory_file_path = ProtocolPath('output_trajectory_path',
# extract_uncorrelated_trajectory.id)
# output_to_store.coordinate_file_path = ProtocolPath('output_coordinate_file',
# converge_uncertainty.id, npt_production.id)
#
# output_to_store.statistics_file_path = ProtocolPath('output_statistics_path',
# extract_uncorrelated_statistics.id)
#
# output_to_store.statistical_inefficiency = ProtocolPath('statistical_inefficiency', converge_uncertainty.id,
# extract_density.id)
#
# schema.outputs_to_store = {'full_system': output_to_store}
return schema